The overall objective of this proposal is to develop a model for studying human immune responses to neoantigens on cell surfaces. To this end we are utilizing techniques that we have developed for induction of human cell-mediated immune responses in vitro to hapten-conjugated cells. We are studying both primary and secondary responses as assessed by T cell proliferation and the induction of T cell-mediated cytotoxicity. Most experiments utilize trinitrophenyl conjugated cells, however, dinitrophenyl and fluorescine conjugates are also studied. Of particular interest is the role of HLA antigens in induction and elicitation of responses to phaten-conjugated cells. Stimulator and responder cell populations are also being characterized functionally, physically, and for cell surface properties. These studies should provide new insights into T cell recognition and responses in humans, and the role of major histocompatibiltiy complex genes and antigens in such responses.